Non-albuminuric Chronic Kidney Disease Research Articles

Urinary Excretion of Biomolecules Related to Cell Cycle, Proliferation, and Autophagy in Subjects with Type 2 Diabetes and Chronic Kidney Disease.

Dysregulation of cell cycle, proliferation, and autophagy plays a pivotal role in diabetic kidney disease. In this study, we assessed urinary excretion of molecular regulators of these processes that mediate their effects via the PI3K/AKT/mTOR pathway in subjects with long-term type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). We included 140 patients with T2D and 20 non-diabetic individuals in a cross-sectional study. Urinary PTEN, Beclin-1, sirtuin 1 (SIRT1), Klotho, fibroblast growth factor 21 (FGF21), and connective tissue growth factor (CTGF) were assessed using ELISA. Patients with T2D, when compared to control, demonstrated increased excretion of PTEN, Beclin-1, SIRT1, FGF21, CTGF, and decreased urinary Klotho (all p < 0.05). In the diabetic group, PTEN, FGF21, and CTGF were significantly higher in patients with declined renal function, while Klotho was lower in those with elevated albuminuria. FGF21 and PTEN correlated inversely with the estimated glomerular filtration rate. There was a negative correlation between Klotho and urinary albumin-to-creatinine ratio. In multivariate models, Klotho and PTEN were associated with albuminuric CKD independently. The results provide further support for the role of PTEN, BECN1, FGF21, Klotho, and CTGF in development albuminuric and non-albuminuric CKD in diabetes.

CVD risk in non-albuminuric chronic kidney disease in hypertensive, non-diabetic subjects: A post-hoc analysis from SPRINT.

The risks associated with non-albuminuric chronic kidney disease (CKD) have been investigated in diabetes mellitus but not in hypertensive patients. The objective of this study was to investigate the risks associated with non-albuminuric CKD in treated hypertensive patients in the Systolic Blood Pressure Intervention Trial (SPRINT) population. Based on baseline albuminuria status (urine albumin/creatinine ratio [UACR], ≥30 or <30 mg/g) and the levels of estimated glomerular filtration rate ([eGFR], ≥60, 45-59, or <45 mL/min/1.73 m2), participants were classified into six subgroups to assess the risks associated with the primary outcome and mortality. The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or mortality from cardiovascular causes. During a median follow-up of 3.26 years in 8,866 hypertensive patients, there were 352 deaths and 547 participants with the primary outcome. In adjusted Cox regression analysis using non-CKD and non-albuminuria (eGFR ≥60 mL/min/1.73 m2 combined with UACR <30 mg/g) as reference, albuminuria whether combined with CKD or not, showed significantly higher risk of both primary outcome and all-cause mortality in the total population. Whereas, non-albuminuria only combined with eGFR <45 mL/min/1.73 m2 showed significantly higher risk of both primary outcome and all-cause mortality in the intensive-therapy group. Non-albuminuric CKD did have higher risk of all-cause and CVD mortality only if the eGFR <45 mL/min/1.73 m2. Increased albuminuria conferred higher risk of primary outcome and all-cause mortality irrespective the levels of eGFR. ClinicalTrials.gov, number: NCT01206062.

Soluble α-Klotho levels, glycemic control and renal function in US adults with type 2 diabetes

AimsSoluble Klotho (s-Klotho) is associated with chronic kidney disease (CKD) and aging, but little is known on its relationship with chronic micro- and macro-vascular complications of type 2 diabetes and glycemic control. Here, we evaluate the association between s-Klotho levels, glycemic control and renal function in patients with type 2 diabetes (T2D).MethodsThis is a cross-sectional study including 2989 patients with T2D and available s-Klotho measurements from the 2007–2016 cycles of the National Health and Nutrition Examination Survey (mean ± SE, age: 60.0 ± 0.2 years, BMI 33.3 ± 0.2 kg/m2, 46.7 ± 1.3% female). Determination of s-Klotho concentrations was performed with a sandwich ELISA test.ResultsPatients with higher s-Klotho levels were younger, more frequently female and had a lower prevalence of CKD and higher HbA1c levels. In multivariable linear regression models adjusting for age, race-ethnicity and BMI, both estimated glomerular filtration rate (B = 2.21, 95% CI 1.41–3.01, p < 0.001) and hemoglobin A1c (B = 37.38, 95% CI 28.91–45.86, p < 0.001) were positively associated with s-Klotho, while no significant association was found with cardiovascular disease. Results were confirmed when analyses were performed in men and women separately. No significant differences were identified between patients with an albuminuric or non-albuminuric CKD phenotype.Conclusionss-Klotho levels are dependent on kidney function and glycemic control in patients with T2D. Additional studies elucidating the mechanisms linking glycemic control and s-Klotho levels and exploring their predictive ability of clinically meaningful outcomes in patients with diabetes are needed.

Examining the factors contributing to the association between non-albuminuric CKD and a low rate of kidney function decline in diabetes.

Background:Studies have shown that among people with diabetes, those with non-albuminuric chronic kidney disease (CKD) have a slower rate of reduction in renal function than do those with normal renal function. This suggests the presence of protective factors, the identification of which may open up targets for intervention. The aim of this study was to identify protective clinical factors and nonclinical biomarkers that contribute to the association between non-albuminuric CKD and the low rate of progression of CKD.Methods:We tested for significant associations of several clinical factors and 33 nonclinical biomarkers with (1) normoalbuminuria and (2) a low rate of CKD progression among participants with diabetes and CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Factors significantly associated with both normoalbuminuria and a low rate of CKD progression were assessed in linear regression to estimate their potential contributions to the association between non-albuminuric CKD and rate of CKD progression.Results:Systolic blood pressure (SBP), glycated A1c (HbA1c), estimated glomerular filtration rate (eGFR) and six biomarkers [β-trace protein (BTP), kidney injury molecule (KIM-1), fibrinogen, fractalkine, brain natriuretic peptide (BNP) and high-sensitivity troponin-T (hsTnT)] were associated with both normoalbuminuria and a low rate of eGFR decline. The univariate β-coefficient for normoalbuminuria was 0.93 [95% confidence interval (CI): 0.82, 1.05]. When all associated factors and biomarkers were included, the regression coefficient decreased to 0.54 (95% CI: 0.40, 0.67). The factors that contributed to the association between non-albuminuric CKD and low rate of eGFR were lower levels of SBP, HbA1c, BTP, KIM-1, hsTnT, BNP, fibrinogen and fractalkine.Conclusion:Lower levels of SBP and biomarkers that have pro-inflammatory and vascular modulating features may explain up to 40% of the association between non-albuminuric CKD and low rate of CKD progression. Further investigation of these biomarkers may lead to therapeutic interventions.

MODY5 Hepatocyte Nuclear Factor 1ß (HNF1ß)-Associated Nephropathy: experience from a regional monogenic diabetes referral centre in Singapore.

From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.

Non-albuminuric chronic kidney disease in diabetes: A different approach?

Background & objectives: Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukaemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment-free remission (TFR) with generic imatinib. This study attempted to determine the feasibility and efficacy of TFR in patients on generic Imatinib. Methods: In this single-centre prospective Generic Imatinib-Free Trial-in-CML-CP study, twenty six patients on generic imatinib for ≥3 yr and in sustained deep molecular response (BCR ABLIS ≤0.01% for more than two years) were included. After treatment discontinuation, patients were monitored with complete blood count and BCR ABLIS by real-time quantitative PCR monthly for one year and three monthly thereafter. Generic imatinib was restarted at single documented loss of major molecular response (BCR ABLIS>0.1%). Results: At a median follow up of 33 months (interquartile range 18.7-35), 42.3 per cent patients (n=11) continued to be in TFR. Estimated TFR at one year was 44 per cent. All patients restarted on generic imatinib regained major molecular response. On multivariate analysis, attainment of molecularly undetectable leukaemia (>MR5) prior to TFR was predictive of TFR [P=0.022, HR 0.284 (0.096-0.837)]. Interpretation & conclusions: The study adds to the growing literature that generic imatinib is effective and can be safely discontinued in CML-CP patients who are in deep molecular remission.

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-AlbuminuricDiabetic Kidney Disease.

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; albuminuria and eGFR <60 mL/min/1.73 m2. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Risk of Rapid Kidney Function Decline, All-Cause Mortality, and Major Cardiovascular Events in Nonalbuminuric Chronic Kidney Disease in Type 2 Diabetes.

We aimed to investigate the rate of progression of nonalbuminuric chronic kidney disease (CKD) to end-stage kidney disease (ESKD) or death or major cardiovascular events (MACE) compared with albuminuric and nonalbuminuric phenotypes. We included 10,185 participants with type 2 diabetes enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Based on baseline albuminuria and estimated glomerular filtration rate (eGFR), participants were classified as having no kidney disease (no CKD), albuminuria only (albuminuric non-CKD), reduced eGFR only (nonalbuminuric CKD), or both albuminuria and reduced eGFR (albuminuric CKD). The rate of eGFR decline and hazard ratios (HRs) for ESKD or death or MACE were calculated. For individuals with no CKD and those with nonalbuminuric CKD, the rates of eGFR decline were -1.31 and -0.60 mL/min/year, respectively (P < 0.001). In competing-risks analysis (no CKD as the reference), HRs for ESKD indicated no increased risk for nonalbuminuric CKD (0.76 [95% CI 0.34, 1.70]) and greatest risk for albuminuric CKD (4.52 [2.91, 7.01]). In adjusted Cox models, HRs for death and MACE were highest for albumuniuric CKD (2.38 [1.92, 2.90] and 2.37 [1.89, 2.97], respectively) and were higher for albuminuric non-CKD (1.82 [1.59, 2.08] and 1.88 [1.63, 2.16], respectively) than for those with nonalbuminuric CKD (1.42 [1.14, 1.78] and 1.44 [1.13, 1.84], respectively). Those with nonalbuminuric CKD showed a slower rate of decline in eGFR than did any other group; however, these individuals still carry a greater risk for death and MACE than do those with no CKD.

Risk factors and urinary biomarkers of non-albuminuric and albuminuric chronic kidney disease in patients with type 2 diabetes.

BACKGROUNDA number of recent studies indicate a transformation in the natural course of chronic kidney disease (CKD) in type 2 diabetes (T2D) patients: an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria. It has been suggested that albuminuric and non-albuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIMTo identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.METHODSThree hundred sixty patients with T2D duration ≥ 10 years were included in this observational cross-sectional study. The associations of a panel of demographic and clinical characteristics, complications, comorbidities, and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed. The urinary excretion of nephrin and podocin, two podocyte-specific markers, and WAP-four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial fibrosis, was determined by ELISA in comparison with healthy controls.RESULTSNon-albuminuric CKD was associated with age ≥ 65 years (P = 0.0001), female sex (P = 0.04), diabetes duration ≥ 15 years (P = 0.0009), and the use of diuretics (P = 0.0005). Male sex (P = 0.01), smoking (P = 0.01), waist-to-hip ratio >1.0 (P = 0.01) and hemoglobin A1c (HbA1c) > 8.0% (P = 0.005) were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate (eGFR). Duration of diabetes ≥ 15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased eGFR (both P = 0.01). In multivariate logistic regression analysis, age, HbA1c, female sex and diuretics were significant predictors for reduced eGFR, while waist-to-hip ratio, HbA1c and male sex were associated with elevated urinary albumin-to-creatinine ratio (UACR). Excretion of nephrin and podocin was increased in patients with albuminuria, regardless of decline in renal function (P < 0.001), correlating positively with UACR. The urinary excretion of WFDC-2 was markedly higher in men than in women (P < 0.000001). Men with T2D demonstrated increased WFDC-2 levels independently of the CKD pattern (all P < 0.05). In T2D women, WFDC-2 excretion was increased in those with reduced renal function (P ≤ 0.01), correlating negatively with eGFR.CONCLUSIONThe data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study

Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) indiabetes. However, the frequency with which itprogresses to end-stage kidney disease (ESKD) isunknown. Multicenter prospective cohort study. We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Urinary albumin and protein excretion. Incident ESKD, CKD progression (ESKD or≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. Mean eGFR at baseline was 41.2mL/min/1.73m2. Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were-0.17,-1.35,-2.74, and-4.69mL/min/1.73m2, respectively. We were unable to compare the results with healthy controls. In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lowerrisk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population.

Albuminuric and non-albuminuric chronic kidney disease in type 1 diabetes: Association with major vascular outcomes risk and all-cause mortality

AimsAlbuminuric and non-albuminuric phenotypes of chronic kidney disease (CKD) may have different cardiovascular risk and survival in type 1 diabetes (T1DM). Herein we estimated risk of major vascular outcomes by the EURODIAB PCS score and determined all-cause mortality rate in 774 T1DM according to CKD phenotypes. MethodsWe evaluated the distribution of CKD phenotypes [no CKD, stages 1–2, non-albuminuric stage ≥3 (Alb−CKD), albuminuric stage ≥3 (Alb+CKD)], the EURODIAB risk score for major vascular outcomes [low- (LS), intermediate- (IS), and high- (HS) risk] and all-cause mortality over a follow-up of 8.25 ± 2.34 years. ResultsOut of 774 subjects, 692 (89.4%) had no CKD, 53 (6.8%) CKD stages 1–2, 17 (2.2%) Alb−CKD and 12 (1.6%) Alb+CKD; 466 (60.2%) had LS, 205 (26.5%) IS and 103 (13.3%) HS. Distribution of HS was: no CKD, 9.1%; CKD stages 1–2, 34.0%; Alb−CKD, 64.7%; Alb+CKD, 91.7% (P < 0.0001). Mortality increased from no CKD, 3.0%; to stages 1–2, 15.1% (HR 4.504); Alb−CKD, 29.4% (8.573); Alb+CKD, 50.0% (20.683, P < 0.0001). Accounting for age and sex, HRs for mortality compared to no CKD were: CKD stages 1–2, 3.84 (P = 0.001); Alb−CKD, 2.97 (P = 0.046); Alb+CKD, 7.44 (P < 0.0001). Adjusting for sex and the EURODIAB score, HRs for mortality compared to no CKD were: CKD stages 1–2, 2.57 (P = 0.027); Alb−CKD, 2.77 (P = 0.058); Alb+CKD, 4.58 (P = 0.003). ConclusionsIn our T1DM cohort, one fifth of those with CKDs were non-albuminuric. This phenotype was associated with higher risk of major outcomes and similar rate of mortality as compared to CKD stages 1–2. The greatest risk and highest mortality occur in patients with Alb+CKD.

Nonalbuminuric chronic kidney disease: A dominant presentation in noncommunicable disease population of rural central India.

Background:India has largest number of people with diabetes mellitus (DM), and hypertension (HTN) is expected to double in next 25 years, which are common causes of chronic kidney disease (CKD). The focus for prevention of end-stage renal disease has shifted to detection of the iceberg of DM and HTN and its adequate control. Prevalence studies of CKD in India rural community are lacking.Methodology:We did community-based cross-sectional study with 3 monthly diagnostic camps in adults ≥20 years (n = 6278), from 13 villages for early detection of CKD in rural population around Sevagram in a group of noncommunicable disease (NCD) with DM, HTN, ischemic heart diseases (IHD), and stroke in year 2015–2016.Results:Study achieved 87% (5440/6278) coverage for albuminuria screening. Prevalence of CKD in NCD population was 19.6% (220/1121) where 86% (181/220) were nonalbuminuric CKD. Prevalence of persistent albuminuria in the study population was 0.8% (45/5440); in NCD population (DM, HTN, IHD, and stroke), it was 2.8% (31/1121). Prevalence of CKD was 19% in HTN and 18.9% in diabetes. The prevalence of nonalbuminuric versus albuminuric CKD was 17.1% versus 1.9% (9 times) in hypertensive individuals and 11.3% versus 7.5% (1.5 times) in individuals with DM.Conclusion:Predominance of nonalbuminuric CKD in NCD participants raises suspicion of CKD with undetermined risk factors. Further studies are needed to find the prevalence of nonalbuminuric CKD in overall population and to find out if exposure of pesticides, chemical fertilizers over long duration play an important role in agrarian rural community.

PP.07.33] HIGH PREVALENCE OF RENAL DYSFUNCTION AND ALBUMINURIA IN PATIENTS WITH ARTERIAL HYPERTENSION AND DIABETES MELLITUS IN HOSPITAL CLINICAL PRACTICE

Objective: Chronic kidney disease (CKD) is recognized as an independent cardiovascular disease (CVD) risk state. Arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) are leading risk factors for both CVD and CKD. The aim of the study was to assess the prevalence of decreased glomerular filtration rate (GFR) and high/ very high albuminuria in patients with AH and T2DM. Design and method: In 319 patients with AH and T2DM admitted in city clinical hospital (37% men, age 65 ± 11 years (M ± SD), body mass index 30 ± 7 kg/m2, blood pressure 135 ± 16/80 ± 9 mmHg, median AH duration 12 years (interquartile range 10;15), T2DM duration 10 years (4;15), dyslipidemia 70%, chronic heart failure 50%, anemia 28%, atrial fibrillation 20%) GFR was assessed by CKD-EPI equation and albuminuria – by albumin/creatinine ratio (ACR) in spot urine morning sample. Results: GFR<60 ml/min/1.73 m2 was revealed in 127 (39.8%) patients, wherein GFR in the range of 45-<60, 30-<45, 15-<30, <15 ml/min/1.73 m2 was found in 18, 17, 5 and 0.6% respectively. ACR>30 mg/g was detected in 123 (39%) of patients, wherein ACR in the range 30-<300 and >300 mg/g was found in 29 and 10%. CKD criteria (GFR<60 ml/min/1.73 m2 and/or ACR>30 mg/g) were detected in 182 (57%) patients. Non-albuminuric CKD (GFR<60 ml/min/1.73 m2 without albuminuria) was found in 59 (18.5%) patients, isolated (without GFR decrease<60 ml/min/1.73 m2) high/ very high albuminuria - in 55 (17%) patients, combined decreased GFR and high/very high albuminuria – in 68 (22%) patients. Patients with vs without albuminuria were older (67.2 ± 10.8 vs 63.7 ± 10.7 years), more aware of kidney diseases (59 vs 41%), had lower level of hemoglobin (122 ± 23 vs 130 ± 21 g/l), p < 0.05 for all. Patients with vs without CKD criteria were older (67 ± 10 vs 60 ± 11 years), had higher prevalence of anemia (34 vs 10%), heart failure (55 vs 32%). Conclusions: High prevalence (57%) of CKD criteria was revealed in hospitalized patients with AH and T2DM. GFR<60 ml/min/1.73 m2 was found in 39.8% of patients, ACR>30 mg/g – in 39%, combined decreased GFR and high/ very high albuminuria – in 22% of patients.

Risks of progression to end-stage renal disease among type 2 diabetic patients with albuminuric and non-albuminuric chronic kidney disease

Risks of progression to end-stage renal disease among type 2 diabetic patients with albuminuric and non-albuminuric chronic kidney disease

The Presence and Consequence of Nonalbuminuric Chronic Kidney Disease in Patients With Type 1 Diabetes.

This study investigated the prevalence of nonalbuminuric chronic kidney disease in type 1 diabetes to assess whether it increases the risk of cardiovascular and renal outcomes as well as all-cause mortality. This was an observational follow-up of 3,809 patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study. All patients were Caucasians and thoroughly examined at baseline. Their mean age was 37.6 ± 11.8 years and duration of diabetes 21.2 ± 12.1 years. Follow-up data on cardiovascular and renal outcomes and mortality were retrieved from registers. During 13 years of median follow-up, 378 developed end-stage renal disease, 415 suffered an incident cardiovascular event, and 406 died. At baseline, 78 (2.0%) had nonalbuminuric chronic kidney disease. This was associated with older age, female sex, history of retinal laser treatment, cardiovascular events, and the number of antihypertensive drugs in use, but not with blood pressure levels or specific antihypertensive agents. Nonalbuminuric chronic kidney disease did not increase the risk of albuminuria (hazard ratio [HR] 2.0 [95% CI 0.9-4.4]) or end-stage renal disease (HR 6.4 [0.8-53.0]) but did increase the risk of cardiovascular events (HR 2.0 [1.4-3.5]) and all-cause mortality (HR 2.4 [1.4-3.9]). The highest risk of cardiovascular and renal end points was observed in the patients with albuminuria. Nonalbuminuric chronic kidney disease is not a frequent finding in patients with type 1 diabetes, but when present, it is associated with an increased risk of cardiovascular morbidity and all-cause mortality but not with renal outcomes.

Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus

Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes

OBJECTIVETo examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.RESEARCH DESIGN AND METHODSSerial (3–5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine.RESULTSMedian and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD.CONCLUSIONSIn patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications.